Systems and methods for selecting stimulation sites and applying treatment, including treatment of symptoms of Parkinson&#39;s disease, other movement disorders, and/or drug side effects

ABSTRACT

Methods and systems for treating movement disorders are disclosed. A method in accordance with one embodiment can include determining that the movement disorder affects the patient&#39;s gait, oral functioning, and/or other functioning, and applying electrical stimulation proximate to the interhemispheric fissure, the Sylvian fissure, or between the two fissures, respectively. In another embodiment, the method can include selecting at least one neural process from among a plurality of processes sequentially carried out by a patient to cause a muscle movement in the patient (e.g., a planning process, an initiation process, and an execution process), and applying electrical stimulation to a location of the patient&#39;s brain associated with the at least one neural process.

TECHNICAL FIELD

The present invention is directed generally toward systems and methodsfor selecting stimulation sites and treating symptoms of Parkinson'sdisease and other movement disorders, and/or drug side effects, forexample, via electrical stimulation at the selected sites.

BACKGROUND

A wide variety of mental and physical processes are controlled orinfluenced by neural activity in particular regions of the brain. Forexample, various physical or cognitive functions are directed oraffected by neural activity within the sensory or motor cortices. Acrossmost individuals, particular areas of the brain appear to have distinctfunctions. In the majority of people, for example, the areas of theoccipital lobes relate to vision; the regions of the left interiorfrontal lobes relate to language; portions of the cerebral cortex appearto be consistently involved with conscious awareness, memory, andintellect; and particular regions of the cerebral cortex, the basalganglia, the thalamus, and the motor cortex cooperatively interact tofacilitate motor function control.

Many problems or abnormalities with body functions can be caused bydamage, disease, and/or disorders in the brain. For example, Parkinson'sDisease (PD) is related to the degeneration or death of dopamineproducing neurons in the substantia nigra region of the basal ganglia inthe brain. Dopamine is a neurotransmitter that transmits signals betweenareas of the brain. As the neurons in the substantia nigra deteriorate,the reduction in dopamine causes abnormal neural activity that resultsin a chronic, progressive deterioration of motor function control.Conservative estimates indicate that PD may affect more than one millionindividuals in the United States alone.

PD patients typically exhibit one or more of four primary symptoms. Oneprimary symptom is a tremor in an extremity (e.g., a hand) that occurswhile the extremity is at rest. Other primary symptoms include ageneralized slowness of movement (bradykinesia); increased musclerigidity or stiffness (rigidity); and gait or balance problems (posturaldysfunction). In addition to or in lieu of these primary symptoms, PDpatients may exhibit secondary symptoms including: difficulty initiatingor resuming movements; loss of fine motor skills; lack of arm swing onthe affected side of the body while walking; foot drag on the affectedside of the body; decreased facial expression; voice and/or speechchanges; cognitive disorders; feelings of depression or anxiety; and/orother symptoms.

Effectively treating PD or other movement disorders related toneurological conditions can be very difficult. Current treatments for PDsymptoms include drugs, ablative surgical intervention, and/or neuralstimulation. Drug treatments or therapies may involve, for example, theadministration of a dopamine precursor that is converted to dopaminewithin the central nervous system (i.e., Levodopa (L-dopa)). Other typesof drug therapies are also available. Unfortunately, drug therapiesfrequently become less effective or ineffective over time for anundesirably large patient population. A PD patient may require multipledrugs in combination to extend the time period of efficacy of drugtherapies. Drug treatments additionally have a significant likelihood ofinducing undesirable physical side effects; motor function complicationssuch as uncontrollable involuntary movements (dyskinesias) are aparticularly common side effect. Furthermore, drug treatments may induceundesirable cognitive side effects such as confusion and/orhallucinations.

Ablative surgical intervention for PD typically involves the destructionof one or more neural structures within the basal ganglia or thalamusthat have become overactive because of the lack of dopamine.Unfortunately, such neural structures reside deep within the brain, andhence ablative surgical intervention is a very time consuming and highlyinvasive procedure. Potential complications associated with theprocedure include risk of hemorrhage, stroke, and/or paralysis.Moreover, because PD is a progressive disease, multiple deep brainsurgeries may be required as symptoms progressively worsen over time.Although ablative surgical intervention may improve a PD patient's motorfunction, it is not likely to completely restore normal motor function.Furthermore, since ablative surgical intervention permanently destroysneural tissue, the effects of such intervention cannot be readilyadjusted or “fine tuned” over time.

Neural stimulation treatments have shown promising results for reducingsome of the symptoms associated with PD. Neural activity is governed byelectrical impulses or “action potentials” generated in and propagatedby neurons. While in a quiescent state, a neuron is negatively polarizedand exhibits a resting membrane potential that is typically between −70and −60 mV. Through chemical connections known as synapses, any givenneuron receives excitatory and inhibitory input signals or stimuli fromother neurons. A neuron integrates the excitatory and inhibitory inputsignals it receives, and generates or fires a series of actionpotentials in the event that the integration exceeds a thresholdpotential. A neural firing threshold, for example, may be approximately−55 mV. Action potentials propagate to the neuron's synapses and arethen conveyed to other synaptically connected neurons.

Neural activity in the brain can be influenced by neural stimulation,which involves the application of electrical and/or magnetic stimuli toone or more target neural populations within a patient using a waveformgenerator or other type of device. Various neural functions can thus bepromoted or disrupted by applying an electrical current to one or moreregions of the brain. As a result, researchers have attempted to treatcertain neurological conditions, including PD, using electrical ormagnetic stimulation signals to control or affect brain functions.

Deep Brain Stimulation (DBS) is a stimulation therapy that has been usedas an alternative to drug treatments and ablative surgical therapies. InDBS, one or more electrodes are surgically implanted into the brainproximate to deep brain or subcortical neural structures. For treatingPD or other movement disorders, the electrodes are positioned in orproximate to the ventrointermediate nucleus of the thalamus; basalganglia structures such as the globus pallidus internalis (GPi); or theSubthalamic Nucleus (STN). The location of the stimulation site for theelectrodes depends upon the symptoms that a patient exhibits and theseverity of the symptoms.

In a typical DBS system, a pulse generator delivers a continuous oressentially continuous electrical stimulation signal having a pulserepetition frequency of approximately 100 Hz to each of two deep brainelectrodes. The electrodes are may be positioned bilaterally on the leftand right sides of the brain relative to particular neural structuressuch as those indicated above. U.S. Pat. No. 5,883,709 discloses oneconventional DBS system for treating movement disorders.

Although DBS therapies may significantly reduce one or more PD symptoms,particularly when combined with drug treatments, they are highlyinvasive procedures. In general, configuring a DBS system to properlyfunction within a patient requires two time consuming, highly invasivesurgical procedures for implanting the DBS electrodes. Each suchsurgical procedure has essentially the same risks as those describedabove for ablative surgical intervention. Moreover, DBS may not providerelief from some movement disorders.

Motor Cortex Stimulation (MCS) is another type of brain stimulationtreatment that has been proposed for treating Parkinson's Disease. MCSinvolves the application of stimulation signals to the motor cortex of apatient. One MCS system includes a pulse generator connected to a stripelectrode that is surgically implanted over a portion of only the motorcortex (precentral gyrus). The use of MCS to treat PD symptoms isdescribed in Canavero, Sergio, Extradural Motor Cortex Stimulation forAdvanced Parkinson's Disease: Case Report, Movement Disorders (Vol. 15,No. 1, 2000).

Because MCS involves the application of stimulation signals to surfaceregions of the brain rather than deep neural structures, electrodeimplantation procedures for MCS are significantly less invasive and timeconsuming than those for DBS. As a result, MCS may be a safer andsimpler alternative to DBS for treating PD symptoms. Present MCStechniques, however, fail to address or adequately consider a variety offactors that may enhance or optimize the extent to which a patientexperiences short term and/or long term relief from PD symptoms.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1B are flow charts illustrating methods for treating movementdisorders in accordance with an embodiment of the invention.

FIG. 1C is a flow chart illustrating a method for treating drug sideeffects, in accordance with another embodiment of the invention.

FIG. 2 is a partially schematic, left side illustration of a human brainindicating stimulation areas associated with addressing gait-relatedmovement disorder symptoms in accordance with an embodiment of theinvention.

FIG. 3 is a partially schematic, left side illustration of the humanbrain indicating stimulation areas for addressing oral-related movementdisorder symptoms, in accordance with another embodiment of theinvention.

FIG. 4 is a partially schematic, left side illustration of the humanbrain illustrating stimulation locations for addressing movementdisorder symptoms other than those related to a patient's gait and oralactivity.

FIG. 5 is a flow chart illustrating a method for addressing dysfunctionin sequentially-related processes associated with patient movement, inaccordance with an embodiment of the invention.

FIG. 6 is a partially schematic, left side illustration of the humanbrain illustrating sites at which electrical stimulation is provided toaddress dysfunctions associated with planning, initiating, and executingmovements, in accordance with an embodiment of the invention.

FIG. 7 is a left side illustration of the brain illustrating anotherarrangement of electrodes for stimulating brain regions associated withsequentially-related movement processes.

DETAILED DESCRIPTION

The following disclosure describes several embodiments of methods andsystems for treating movement disorders (e.g., Parkinson's Disease (PD))and/or associated symptoms, and/or symptoms associated with drug sideeffects, using cortical stimulation. Several methods and systems forapplying treatment in accordance with embodiments of the invention areset forth and described in FIGS. 1A-7. It will be appreciated that otherembodiments can include additional procedures and/or different featuresthan those shown in FIGS. 1A-7. Additionally, methods and systems inaccordance with several embodiments of the invention may not include allof the features shown in these Figures.

A method for treating movement disorders in accordance with oneembodiment of the invention includes determining that the movementdisorder affects a patient's gait, and applying electrical stimulationto a region of the patient's brain that is proximate to theinterhemispheric fissure of the patient's brain. In another embodiment,the method can include determining that the movement disorder affectsthe patient's oral functioning, and can further include applyingelectrical stimulation to a region of the patient's brain that isproximate to the Sylvian fissure of the patient's brain. In stillanother embodiment, the method can include determining that the movementdisorder affects an aspect of the patient's movement other than thepatient's gait and oral functioning, and can further include applyingelectrical stimulation to a region of the patient's brain that islocated between the interhemispheric fissure and the Sylvian fissure ofthe patient's brain.

Methods in accordance with further aspects of the invention can furtherinclude applying electrical stimulation to both sides of the centralsulcus of the patient's brain, or on a single side of the central sulcusof the patient's brain. Stimulation can be applied ipsilaterally orcontralaterally, in a unipolar manner, and/or in a bipolar manner.

In a still a further aspect of the invention, a method for treatingmovement disorders includes selecting at least one neural process fromamong a plurality of processes sequentially carried out by a patient tocause a muscle movement in the patient. The method can further includeapplying electrical stimulation to a location of the patient's brainassociated with the at least one neural process. For example, the methodcan include selecting the at least one neural process from among aplanning process, an initiation process, and an execution process. Themethod can further include applying electrical stimulation to thepatient's dorsolateral prefrontal cortex, interhemispheric fissure,primary motor strip, or premotor cortex of the patient's brain.

In yet another embodiment, electrical stimulation can be used to addressaspects of a patient's functioning that are attributed to drug intake(e.g., drug side effects). A method in accordance with one suchembodiment includes determining what aspect of a patient's functioningis affected by the patient's drug intake, and applying electricalstimulation to a region of the brain that is associated with the aspectof the patient's functioning. In particular embodiments, this method canbe used to address cognitive and/or motor dysfunctions resulting as sideeffects from the patient's intake of drugs that target Parkinson'sdisease and/or other movement disorders.

FIG. 1A is a block diagram illustrating a method 100 for treating apatient's movement disorder(s) and/or associated symptoms. The movementdisorder may be associated with Parkinson's disease (PD) and/or otherconditions, including other pathological conditions. In process portion102, the method 100 includes determining what aspect of a patient'smotion the movement disorder affects. For example, the movement disordermay primarily affect the patient's gait, or the patient's oralfunctions, (e.g., the patient's speech, chewing, and/or swallowingactivities). Other patients may have other aspects of their motionaffected. For example, other patients may experience tremors at anextremity, and/or difficulties with arm movement, and/or midlinesymptoms, including difficulties with postural stability. Most, if notall, of the foregoing symptoms can be diagnosed and distinguished fromeach other in a relatively straightforward manner using clinicalexaminations and/or patient reports.

In process portion 104, the method 100 includes applying electricalstimulation to a region of the patient's brain that is associated withthe particular aspect of the patient's motion identified in processportion 102. In particular, different parts of the brain may beassociated with different aspects of the patient's movements, and themethod 100 can include stimulating or preferentially stimulating thoseareas most closely associated with the particular symptoms experiencedby the patient. Further details of the brain areas that can bestimulated in accordance with embodiments of the invention are describedbelow with reference to FIG. 1B.

Referring now to FIG. 1B, process portion 102 can include determiningwhether or not the patient's gait is affected (process portion 106) and,if it is, stimulating the patient's brain closer to the interhemisphericfissure than to the Sylvian fissure (process portion 108). In processportion 110, the process 100 can include determining if the patient'soral activity is affected and, if it is, stimulating the patient's braincloser to the Sylvian fissure than to the interhemispheric fissure(process portion 112). If a practitioner determines that activitiesother than the patient's gait and oral functions are affected (processportion 114), the practitioner can stimulate the patient's brain betweenthe Sylvian fissure and the interhemispheric fissure, with a reducedpreference for proximity to either fissure.

In other embodiments, methods similar in part to those described abovewith reference to FIGS. 1A and 1B can be used to address additionaland/or other types of symptoms. For example, FIG. 1C illustrates aprocess 117 that includes determining what aspect of a patient'sfunctioning is affected by the patient's chemical substance or drugintake (process portion 118). The process can further include applyingelectrical stimulation to one or more regions of the patient's brainthat are associated with the aspect of the patient's functioning(process portion 119).

In further particular examples, the drug or drugs taken by the patientcan include drugs taken to address movement disorders (e.g., PD) butthat have side effects on the patient's cognitive and/or motorfunctioning. L-dopa is one such drug that can induce unwanteddyskinesias (e.g., chorea and/or dystonia). The dyskinesias can includepeak-doses dyskinesias (associated with peak levels of L-dopa in thebrain), “off” dyskinesias (which occurs when the effects of L-dopa wearoff), and/or diphasic dyskinesias (associated with changes in the plasmalevel of L-dopa, typically at the beginning and/or end of a dose). Otherdrugs or chemical substances that may produce unwanted side effects caninclude Sinemet, Mirapex and glial-derived neurotrophic factor (GDNF).

The site(s) of the patient's brain selected for stimulation can dependon the aspects of the patient's functioning to be addressed. Forexample, if the effects of the drug are related to the patient's motion,the stimulation can be applied to the primary motor cortex, premotorcortex and/or supplemental motor area. If the effects relate to thepatient's cognitive abilities, the stimulation can be applied to theprefrontal cortex. Illustrations of representative stimulation systemsand stimulation sites associated with the foregoing method are describedbelow with reference to FIGS. 2-4.

FIG. 2 is a schematic illustration of a neural stimulation system 230for treating symptoms of PD and/or other neurologic dysfunction (e.g.,movement, cognitive and/or emotional dysfunction) in accordance with anembodiment of the invention. The neural stimulation system 230 caninclude a pulse generator 235 configured to deliver stimulation signalsto a patient 200 via one or more electrode devices 231 implanted in thepatient 200. Accordingly, the pulse generator 235 can be coupled to theelectrode device 231 by one or more leads 233. The pulse generator 235may further be configured for wireless and/or wire-based communicationwith a control system 234, which can in turn include one or morecontrollers 240 (shown in FIG. 2 as a first controller 240 a and asecond controller 240 b). Depending upon embodiment details, the system230 may further include one or more patient monitoring units 250configured to detect, monitor, indicate, measure, and/or assess theseverity of particular types of patient symptoms or deficits. Furtherdetails of the foregoing system components are described below.

The electrode device 231 may include one or more electrically conductivecontacts 232 carried by one or more substrates 236, for example, in amanner described in U.S. application Ser. No. 10/742,579, entitled“Methods and Apparatus for Applying Electrical Stimulation andManufacturing Same,” filed on Dec. 18, 2003, and incorporated herein byreference. The contacts 232 are configured to provide, deliver, and/orapply stimulation signals to particular cortical regions of thepatient's brain 210 and/or neural populations synaptically connectedand/or proximate thereto. The electrode device 231 may alternatively oradditionally include one or more penetrating, depth, deep brain, and/ornerve cuff electrodes. One or more of the contacts 232 may be configuredas a signal return contact (i.e., a contact that provides a currentreturn path for electrical continuity), and may be positioned relativeto a variety of locations within and/or upon the patient's body tofacilitate unipolar stimulation. This function may also be provided byother structures (e.g., a housing or other portion of the electrodedevice 231). In another embodiment, one or more of the contacts 232 canbe configured to provide bipolar signals (e.g., the return contact canbe positioned at or proximate to the stimulation site).

The characteristics and/or placement of the electrode device 231 maydepend upon the nature of patient's underlying disorder(s), functionaldeficit(s), and/or the type and/or severity of symptoms that the patient200 experiences or exhibits. In a particular embodiment, one or moreportions of the electrode device 231 may be surgically implanted toapply, deliver, and/or direct stimulation signals to target neuralpopulations within the patient's brain, for example, in a manneridentical, essentially identical, or analogous to that described in U.S.application Ser. No. 10/732,731, entitled “System and Method forTreating Parkinson's Disease and Other Movement Disorders,” filed onDec. 9, 2003, and/or U.S. application Ser. No. 09/802,808, filed on Mar.8, 2001, both incorporated herein by reference.

The electrode device 231 receives stimulation signals from the pulsegenerator 235, which may include hardware and/or software for generatingand outputting stimulation signals in accordance with internalinstruction sequences and/or in response to control signals, commands,instructions, and/or other information received from the controller(s)240. The pulse generator 235 may include a power supply and a pulseunit, a programmable computer medium, and a communication unit. Thepower supply may include a battery or other type of power storagedevice. The pulse unit may include circuitry for generating pulsesequences that may be defined or characterized in accordance withvarious stimulation signal parameters. Stimulation can be provided at acurrent of from between 2 and 20 milliamps and at a frequency of 0.5 Hz,1-2 Hz, or higher. In some embodiments, a generally low frequency signal(e.g., from about 0.5-10 Hz) can result in longer lasting beneficialeffects and/or greater relief from adverse symptoms. In someembodiments, it is also beneficial to have a “reset” period. Forexample, the patient can undergo stimulation for a period of seconds,minutes, hours or days, followed by a period of no stimulation (e.g.,for a number of seconds, minutes or hours) before stimulation beginsagain.

In a particular embodiment, the frequency of the stimulation signal canbe varied in a random, aperiodic manner centered, for example, at a meanfrequency of 5 Hz. The voltage or amplitude of the signal can beconstant or can be varied in a variety of manners, including randomvariation and/or occasional high amplitude bursts. The range offrequencies may focus on the lower frequency ranges (e.g., from 1-2 Hz)and, for biphasic pulses, the first phase pulse width can be varied. Inparticular embodiments, the frequency can be varied in a mannerindicated to break up oscillatory patterns that may exist betweencortical and subcortical structures. Such signal patterns have beenassociated with Parkinson's disease and may be associated with othermovement disorders as well. Aspects of these patterns are described byTimmermann et al. in an article titled, “The Cerebral OscillatoryNetwork of Parkinsonian Resting Tremor” (Brain (2003), 126, 199-212),incorporated herein in its entirety by reference. Further aspects ofapplicable signal parameters are described in co-pending U.S.application Ser. No. 10/782,526, filed Feb. 19, 2004 and incorporatedherein in its entirety by reference.

Each element of the pulse generator 235 may be incorporated or embeddedin a surgically implantable case or housing. Depending upon embodimentdetails, the pulse generator 235 may be surgically implanted in thepatient 200 at a subclavicular location 202. Alternatively, the pulsegenerator 235 may be surgically implanted above the patient's neck, forexample, in the patient's skull at a location posterior to the patient'sear and/or proximate to an electrode implantation site. A surgicallyformed tunnel or path may route the lead or leads 233 that couple thepulse generator 235 to the electrode device 231, in a manner understoodby those skilled in the art. Additionally, one or more electricallyconductive portions of the pulse generator case or housing may serve asa return electrode for electrical current.

The controllers 240 may comprise hardware and/or software configured todirect and/or manage the local operation of the pulse generator 235. Forexample, the controllers may be configured to communicate controlsignals, commands, instructions, parameter settings and/or ranges,and/or other information to the pulse generator 235. Accordingly, thecontrollers 240 may each include a processing unit 241, a programmableor other computer-readable medium 242, and a communications unit 243.The communications unit 243 may include a user interface thatfacilitates communication with devices external to the pulse generator235, for example, through telemetric signal transfer. Thecomputer-readable medium 242 may comprise hardware and/or memoryresident software. The computer-readable medium 242 may storeoperational mode information and/or program instruction sequences thatmay be selected and/or specified by a practitioner. The pulse generator235 may be configured to deliver stimulation signals to particularelectrode devices 231 and/or to specific electrical contacts 232 of theelectrode device 231 on a selective basis at any given time, e.g., in amanner identical, essentially identical, or analogous to that describedin U.S. application Ser. No. 09/978,134, entitled “Systems and Methodsfor Automatically Optimizing Stimulation Parameters and ElectrodeConfigurations for Neuro-Stimulators,” filed on Oct. 15, 2001, andincorporated herein by reference.

The first controller 240 a can include a “full functionality”controller, configured for operation by a medical professional. Thesecond controller 240 b can include a limited or “partial functionality”controller configured for operation by a patient. The second controller240 b may facilitate patient-based selection and/or adjustment ofparticular preprogrammed operating modes and/or neural stimulationsettings. In some embodiments, the first and second controllers 240 a,240 b may be configured for wire-based or wireless communication witheach other. One or both of the controllers 240 may be configured toreceive information from the pulse generator 235 (e.g., the overallstatus and/or performance level of the pulse generator 235).Communication between the control system 234 and the pulse generator 235may facilitate or effectuate specification, selection, and/oridentification of operational modes, instruction sequences, and/orprocedures for treating one or more patient conditions, states, and/orsymptoms associated with PD, other movement disorders, and/or othertypes of neurologic dysfunction in a variety of manners.

The patient monitoring unit 250 may be used to determine the effects ofthe stimulation signals provided by the controller(s) 240, the pulsegenerator 235, and the electrode device(s) 231. Accordingly, the patientmonitoring unit can include any type of device configured to detect,monitor, indicate, estimate, characterize, measure, calculate, and/orassess neural pathway characteristics and/or the nature, level,intensity, magnitude and/or severity of one or more types of patientstates, conditions, deficits, and/or symptoms associated with PD and/orother neurological dysfunctions. For example, a patient monitoring unit250 may include a motion detection system configured to detect patientmovement associated with tremor. A motion detection system may includelight emitting and/or detecting devices and/or accelerometers coupled toparticular patient extremities. In another example, the patientmonitoring unit 250 includes an Electromyography (EMG) system that hasone or more sets of surface or depth electrodes positioned relative toparticular muscle groups for detecting electrical signals correspondingto muscle fiber innervation. In still another example, the patientmonitoring unit 250 includes an Electroencephalography (EEG), anElectrocorticography (ECoG) system, and/or a Magnetoencephalography(MEG) system. In yet another embodiment, the patient monitoring unit 250includes one or more electrode contacts 232 and, optionally, softwareand/or hardware (e.g., signal processing software and/or circuitry)within the pulse generator 235.

In other arrangements, the patient monitoring unit 250 includes a neuralimaging system, for example, a Magnetic Resonance Imaging (MRI), afunctional MRI (fMRI), a Positron Emission Tomography (PET), and/orother type of system. As another example, the patient monitoring unit250 may include one or more electrodes and/or probes (e.g., cerebralbloodflow monitors) positioned upon, proximate, and/or within giventarget neural populations, and associated hardware and/or software fordetecting, presenting, and/or analyzing signals received therefrom.Still further examples of patient monitoring units are described inco-pending U.S. application Ser. No. 10/782,526, previously incorporatedherein by reference.

In addition to illustrating a representative stimulation system 230,FIG. 2 also illustrates a representative placement for the electrodedevice 231. The electrode device 231 shown in FIG. 2 is positioned toprovide stimulation to a patient 200 experiencing a gait-related neuraldysfunction symptom (e.g., foot dragging). In one aspect of thisembodiment, the electrode device 231 is positioned at a selected region217 of the brain 210 located closer to the interhemispheric fissure 211(located behind the plane of FIG. 2) than to the Sylvian fissure 212.The contacts 232 of the electrode device 231 can be located at theprecentral gyrus 214 and/or the postcentral gyrus 215. In some cases, itmay be advantageous to position the electrode device 231 to span thecentral sulcus 213, allowing the practitioner to selectively stimulateeither or both of the precentral gyrus 214 and the postcentral gyrus215. In other cases, the electrode device 231 can be positioned toextend posterior to the post-central sulcus 216. In any of these cases,the contacts 232 can be positioned subdurally or epidurally, dependingon which is most effective for the patient 200. The contacts 232 can belocated ipsilaterally and/or contralaterally with regard to the side ofthe patient 200 exhibiting the targeted symptoms. In at least oneembodiment (e.g., when the patient 200 exhibits gait-related symptoms onboth sides of the body), the practitioner can identify the brainhemisphere primarily associated with the patient's speech, and thenstimulate that hemisphere so as to reduce or even prevent speech-relatedsymptoms while at the same time addressing gait-related symptoms.

The electrode device 231 can include a plurality of contacts 232 thatprovide stimulation at one or more stimulation sites 218. Accordingly,the practitioner can sequentially stimulate at a different site (a) whenit is not clearly evident, except by trial, where stimulation is mosteffective, and/or (b) when the patient 200 benefits from stimulation atmultiple sites. In the latter case, stimulation may also be appliedsimultaneously to multiple sites.

In one aspect of this embodiment, the contacts 232 can be arranged in a2×3 array, and in other embodiments, the contacts 232 can be arranged inarrays having other dimensions, including a single row of contacts 232.Each contact 232 can have a surface area and spacing selected to providestimulation in the desired fashion. For example, in one embodiment, thecontacts 232 have a surface area of about 5 mm², and each contact 232can be spaced apart from its nearest neighbor by about 2.5 mm. In otherembodiments, the size of the contacts 232 and the spacing between thecontacts 232 can be different.

In any of the foregoing embodiments, the electrical stimulation providedby the electrode device 231 can reduce and/or eliminate gait-relatedsymptoms experienced by the patient 200. The electrical stimulationprovided by the electrode device 231 can be selected by the practitionerto provide unipolar and/or bipolar stimulation. As used herein, unipolarstimulation refers generally to stimulation provided by one or morecontacts proximate to a given stimulation site 218 while all thecontacts 232 are at or near the same electrical potential. In this case,a return electrode or contact is provided at a site distal thestimulation site 218, for example, at the implanted pulse generator 235.Conversely, bipolar stimulation, as used herein, refers generally tostimulation provided by at least two contacts 232 positioned proximateto the stimulation site 218, with one of the contacts at a higherelectrical potential than the other. Multiple contacts 232 can bearranged in bipolar pairs, with each pair including one contact 232 at ahigher potential than its pair mate. The pulse control system 234 can beconfigured to provide both unipolar and bipolar stimulation signals tothe electrode device 231. Accordingly, the same electrode device 231 andpulse control system 234 can be used for patients receiving bipolar andunipolar stimulation. Furthermore, the pulse control system 234 can beprogrammed or reprogrammed during treatment to switch between bipolarand unipolar stimulation, when this type of alternation provides or isexpected to provide an additional benefit to the patient.

FIG. 3 is an illustration of the brain 210 with the electrode device 231positioned at a selected region 317 to address oral-related movementdisorder symptoms. Accordingly, the selected region 317 is positionedcloser to the Sylvian fissure 212 than to the interhemispheric fissure211. The contacts 232 can be located proximate to multiple stimulationsites 318, and can provide bipolar and/or unipolar stimulation, in amanner generally similar to that described above. As was also describedabove, the electrode device 231 can be sized, shaped and positioned in amanner that allows the practitioner to selectively stimulate multiplesites, sequentially and/or simultaneously. In one aspect of thisembodiment, the electrode device 231 positioned at or near the Sylvianfissure 212 can have the same size and shape as the electrode device 231positioned at or near the interhemispheric fissure 211 (FIG. 2). Inother embodiments, the size and/or shape of the electrode device 231,and/or the arrangement of contacts 232 can be different depending onwhether the electrode device 231 is selected to address primarilygait-related or oral-related symptoms.

FIG. 4 is an illustration of the brain 210 with the electrode device 231positioned at a selected region 417 to address symptoms other thangait-related symptoms and oral-related symptoms. Accordingly, theelectrode device 231 can be positioned between the interhemisphericfissure 211 and the Sylvian fissure 212. In a particular aspect of thisembodiment, the electrode device 231 and the contacts 232 it carries canbe located approximately midway between the interhemispheric fissure 211and the Sylvian fissure 212, and in other embodiments, the contacts 232can be located more toward one fissure than the other. In any of theseembodiments, the contacts 232 tend not to be located as close to theinterhemispheric fissure 211 as was shown in FIG. 2, or as dose to theSylvian fissure 212 as was shown in FIG. 3.

In still further embodiments, aspects of the arrangements describedabove with reference to FIGS. 2-4 can be combined. For example, if thepatient 200 suffers from multiple symptoms (e.g., gait-related symptoms,oral-related symptoms and other symptoms), then a single electrodedevice 231 can be located over multiple selected regions. In anotherembodiment, the practitioner can implant multiple electrode devices 231at each of the corresponding regions expected to provide aid to thepatient 200. In either arrangement, the electrode(s) 231 expected to benecessary for addressing the patient's symptoms can be implanted in asingle procedure, whether or not all the associated contacts 232 areultimately used.

FIGS. 5-7 illustrate methods for applying electrical stimulation to apatient's brain in accordance with further aspects of the invention.Referring first to FIG. 5, a method 500 in accordance with oneembodiment of the invention includes selecting at least one neuralprocess from among a plurality of sequential neural processes associatedwith causing a muscle movement in the patient (block 502). The neuralprocesses can include a planning process, an initiation process, and/oran execution process. As used herein, the planning process refersgenerally to the neurological process of forming instructions forcarrying out a movement. Initiation refers generally to beginning theplanned movement, and execution refers to fully carrying out the plannedmovement. Each movement executed by a patient generally results from thepatient performing the foregoing three processes in sequence.

In block 504, electrical stimulation is applied to a location of thepatient's brain associated with the at least one neural process selectedin block 502. For example, in many cases, a different specific area ofthe brain is associated with each of the planning, initiation, andexecution processes. Accordingly, the electrical stimulation can beapplied to the location of the patient's brain associated with one ormore of the foregoing processes.

Once the (at least one) target neural process has been selected, thepractitioner can implant an electrode device at least proximate to thearea of the patient's brain associated with the target neural process.FIG. 6 illustrates the brain 210 along with three selected regions 617(shown as a first selected region 617 a, second selected region 617 b,and third selected region 617 c), each associated with one of the targetneural processes. For example, the first selected region 617 a caninclude the dorsal lateral prefrontal cortex 619, which has been shownto be associated with motor task planning. The second selected region617 b can include areas proximate to the interhemispheric fissure 211and anterior to the motor strip 620 (e.g., the supplementary motor area621). In a particular embodiment, the second selected region 617 b canextend into the interhemispheric fissure 211. The third selected region617 c can include the motor strip 620 and can accordingly extendlaterally from the interhemispheric fissure 211 to the Sylvian fissure212. The third selected region 617 c can also include the premotorcortex, a portion of the supplementary motor area 621. The motor strip620 may be stimulated to address symptoms associated with fine motorcontrol, and the premotor cortex may be stimulated to address symptomsassociated with general motor control.

A stimulation system 630 for stimulating the brain 210 can include apulse generator 635 coupled to one or more pulse control systems (notshown in FIG. 6) generally similar to those described above withreference to FIG. 2. In a particular embodiment in which it is desiredto stimulate areas associated with all three neural processes (planning,initiation, and execution), the stimulation system 630 can includeelectrode devices 631 (shown as first, second, and third electrodedevices 631 a, 631 b, and 631 c, respectively) having electricalcontacts 632 located at each of the three selected regions 617 a-617 c,respectively. When the second selected region 617 b extends into theinterhemispheric fissure 211, the second electrode device 631 b can beplaced in the interhemispheric fissure 211 as well. Alternatively, thesecond electrode device 631 b can be located external, (but proximateto) the interhemispheric fissure 211, while still providing stimulationto neural structures located within the interhemispheric fissure 211,e.g., in a manner generally similar to that described in U.S.application Ser. No. ______, entitled “Electrode Configurations forReducing Invasiveness and/or Enhancing Neural Stimulation Efficacy,”filed concurrently herewith and incorporated herein by reference.Corresponding leads 633 a-633 c can be coupled between the pulsegenerator 635 and the electrode devices 631 a-631 c. In otherembodiments, for example, when it is clear that only one or two of theregions 617 a-617 c would benefit from stimulation, fewer electrodedevices 631 can be implanted in a single procedure at fewer than threeregions.

Stimulation signals may be provided to the brain 210 in accordance withany of the parameters described above with reference to FIGS. 2-4. Forexample, the stimulation site can be located on the ipsilateral orcontralateral side of the brain 210 with respect to the location of theimpediment. In some embodiments, the practitioner can stimulate sites atboth hemispheres, either sequentially or simultaneously, depending (forexample) on the particular symptoms exhibited by the patient, and/or theparticular process (e.g., planning, initiation, and/or execution) thepractitioner wishes to address. The frequency, amplitude, pulse widthand other signal parameters can also be varied in manners generallysimilar to those described above to provide effective treatment for thepatient.

In some patients, a defect associated with one of the foregoingsequential processes may predominate. Once the defect associated withthis process has been addressed, defects associated with other processesmay become more evident. In other cases, it may be impossible orimpracticable to identify which process is primarily responsible for thepatient's symptoms, for example, because the processes are typicallyexecuted by the patient in very rapid succession. In any of these cases,the practitioner may implant multiple electrode devices and/or multiplecontacts covering a range of target regions of the brain, and thenstimulate a particular region until the problem with that region isaddressed (or eliminated as a source of symptoms), then move to anotherregion if symptoms associated with that region become evident, or ifstimulation at the first region does not have the desired effect.Stimulation can be provided at multiple sites in a sequential,simultaneous, alternating, random, pseudorandom, and/or intermittentmanner. The multiple electrode devices can be implanted simultaneouslyor serially (e.g., after stimulation with an initial electrode devicehas been completed or determined to be ineffective).

As described above with reference to FIG. 1C, stimulation can also beapplied to the brain to address side effects associated with thepatient's drug intake. Stimulation can be applied to the premotor cortex622, the supplemental motor area 621, and/or the primary motor cortex623 (for motion-related symptoms), and/or the prefrontal cortex 619 (forcognitive symptoms). The benefits of stimulation in these areas caninclude a reduction in drug side effects and/or a reduction inconventional drug doses (so as to produce essentially the same, thesame, or greater therapeutic effect with fewer side effects). Thepatient may also have an increased “on time” (e.g., an increased periodof time during which the drug is providing therapeutic effects) whileexhibiting no side effects or reduced side effects.

FIG. 7 illustrates another arrangement of electrode devices that may besuitable for use when it is not certain which of the foregoing processesthe patient has the most difficulty with, and/or when it is known thatthe patient has difficulty with more than one process. The arrangementcan include two strip-type electrode devices, shown as a first electrodedevice 717 a and a second electrode device 717 b. The first electrodedevice 717 a can be positioned to extend over both the dorsal lateralprefrontal cortex 619 (e.g., the first selected region 617 a), and thesupplementary motor area 621 (e.g., the second selected region 617 b).The second electrode device 717 b can extend over the motor strip 620(e.g., the third selected region 617 c). In one aspect of thisembodiment, each electrode device 717 a, 717 b can include a single rowof contacts 732, and in other embodiments, each electrode device 717 a,717 b can include multiple rows or other arrangements of contacts 732.In any of these embodiments, both electrode devices 717 a, 717 b can becoupled to one or more pulse generators and controllers (not shown inFIG. 7) to selectively provide electrical stimulation to target areaseither simultaneously or sequentially, depending, for example, onwhether the patient exhibits symptoms sequentially or simultaneously.

In other embodiments, the systems described above can be implanted andoperated in still further manners. For example, one or more electrodedevices can be implanted in a manner that places first and secondelectrical contacts proximate to different areas of the patients brain.Electrical stimulation can then be applied simultaneously orsequentially to these areas to treat one or more neural dysfunctions,and the implantation site can be selected in a manner that does notnecessarily require identifying the functional manifestation of theneural dysfunction. In a particular embodiment, the stimulation can beapplied to any two (or more) of the motor cortex, the prefrontal cortexand the supplementary motor area. As used herein, the term motor cortexcan include the primary motor cortex and/or the premotor cortex. Thestimulation can be applied to one or both of the patient's brainhemispheres. In other embodiments, the stimulation can be applied toother multiple locations.

From the foregoing, it will be appreciated that specific embodiments ofthe invention have been described herein for purposes of illustration,but that various modifications may be made without deviating from thespirit and scope of the invention. For example, aspects of the inventiondescribed in the context of particular embodiments can be combined oreliminated in other embodiments. Many of the steps are described abovein a particular order for purposes of illustration, but can be carriedout in other orders as well. Further details of electrode system,techniques for visualizing target implant areas, and techniques forimplanting electrodes are disclosed in the following corresponding U.S.Applications, all of which are incorporated herein by reference: Ser.No. 10/731,731, filed Dec. 9, 2003; Ser. No. 10/910,775, filed Aug. 2,2004; Ser. No. 10/877,830, filed Jun. 25, 2004; and Ser. No. 10/731,852,filed Dec. 9, 2003. Accordingly, the invention is not limited except asby the appended claims.

1-17. (canceled)
 18. A method for treating movement disorders,comprising: determining that the movement disorder affects a patient'soral functioning; and applying electrical stimulation to a region of thepatient's brain that is proximate to the Sylvian fissure of thepatient's brain.
 19. The method of claim 18 wherein applying electricalstimulation includes at least reducing effects of the movement disorderon the patient's oral functioning.
 20. The method of claim 18 whereinapplying electrical stimulation includes applying electrical stimulationto a region of the patient's brain that is closer to the Sylvian fissureof the patient's brain than to the interhemispheric fissure of thepatient's brain.
 21. The method of claim 18 wherein applying electricalstimulation includes applying electrical stimulation at a first sitelocated on a first side of the central sulcus of the patient's brain,and at a second site located on a second side of the central sulcus. 22.The method of claim 18 wherein applying electrical stimulation includesapplying electrical stimulation at a first site and a second site, withboth the first and second sites located on the same side of the centralsulcus of the patient's brain.
 23. The method of claim 18, furthercomprising determining a hemisphere of the brain from which signalsrelated to the patient's oral functioning are transmitted, and whereinapplying electrical stimulation includes applying electrical stimulationto the opposite hemisphere.
 24. The method of claim 18 wherein applyingelectrical stimulation includes applying unipolar electricalstimulation.
 25. The method of claim 18 wherein applying stimulationincludes applying bipolar stimulation.
 26. The method of claim 18wherein applying stimulation includes applying stimulation at multiplesites located within the region of the patient's brain.
 27. The methodof claim 18 wherein applying stimulation includes applying stimulationat a frequency of 0.5 Hz or above.
 28. The method of claim 18 whereinapplying stimulation includes applying stimulation with a frequency thatvaries in at least one of a random, pseudorandom and aperiodic manner.29-67. (canceled)